Toxicogenomics-based Mechanistic Multimedia Exposure Assessment and Child Development

EPA Grant Number: R836155C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R836155
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Center for Research on Early Childhood Exposure and Development in Puerto Rico
Center Director: Alshawabkeh, Akram
Title: Toxicogenomics-based Mechanistic Multimedia Exposure Assessment and Child Development
Investigators: Gu, April Z , Fasullo, Michael , MacIntosh, Helen Suh , Manjourides, Justin , Vulpe, Christopher D. , Weisman, David
Institution: Northeastern University , The State University of New York Polytechnic Institute , University of California - Berkeley , University of Massachusetts - Boston
EPA Project Officer: Louie, Nica
Project Period: September 1, 2015 through August 31, 2019
RFA: Children's Environmental Health and Disease Prevention Research Centers (2014) RFA Text |  Recipients Lists
Research Category: Health , Children's Health

Objective:

Specific Aim 1: Assess the toxicity of individual pollutants and pollutant mixtures found in tap water collected from 40 participants’ homes.

Specific Aim 2: Quantify the toxicity associated with metal and organic carbon extracts from samples of airborne fine particlulate matter (PM2.5).

Specific Aim 3: Analyze mixture toxicity effects of CECs, metals, and other chemicals and chemical metabolites in urine samples of 40 pregnant mothers.

Specific Aim 4: Use measures of toxicity and pollutant concentrations to identify pollutants most responsible for eliciting the observed pathway-specific toxicity impacts. 

Approach:

These challenges motivate this project, which will employ novel in vitro, high throughput screening (HTS) assays to yield new toxicity information needed to reveal the impacts of exposure to complex pollutant mixtures on neonatal and early childhood development in Puerto Rico. These HTS assays will specifically measure translational changes in oxidative stress, DNA damage and inflammation pathways occurring in response to pollutants and pollutant mixtures. Importantly, these pollutants and mixtures are drawn directly from environmental sources, such as water and air, and also from biological matrices like urine, providing information about exposures to chemical mixtures actually occurring in the real-world. Through this approach, we can provide pathway- and sample-specific fingerprints of pollutant exposures and their effects that can inform epidemiological studies, including CRECE Projects 1 and 3. These cross-project collaborations will enable CRECE to perform health effect analyses for pollutant mixtures identified as toxic by the HTS and to examine the association of exposure biomarkers with neonatal and early childhood health outcomes.

We will use this approach to achieve four specific aims: (1) assess the toxicity of individual pollutants and pollutant mixtures found in tap water collected from 40 participants’ homes; (2) quantify the toxicity associated with metal and organic carbon extracts from airborne fine particle (PM2.5) samples collected as part of Project 1; (3) analyze mixture toxicity effects of CECs, metals, and other chemicals and chemical metabolites in urine samples of 40 pregnant mothers, and (4) use toxicity measures from Aims 2 and 3 and pollutant concentrations measured in Projects 1 and 3 to identify pollutants most responsible for eliciting the observed pathway-specific toxicity impacts.

The outcomes of this project will help to inform strategies to minimize health impacts from multiple exposures on Puerto Rico children, a highly exposed population that experiences disproportionate levels of childhood illness, as well as children in the U.S.

Rationale:

Children in the northern coast of Puerto Rico are exposed to a complex mix of environmental contaminants. The region has over 200 hazardous waste sites, including 16 active Superfund sites, resulting in contaminated water resources. Air pollution from refineries, power plants, motor vehicles, and large ships at ports is also very high, and made worse by Saharan dust storms crossing the Atlantic which have increased in frequency in recent decades. Children in highly polluted areas like Puerto Rico rarely experience any of these exposures in isolation, yet health effect studies associated with exposure to chemical mixtures are rare, with most research instead focusing on single chemicals. Significant challenges remain in understanding the complex risks that pollutant mixtures and their metabolites pose for human health. Novel approaches to examining the impacts of pollutant mixtures are critical to developing preventative strategies to reduce the burden of disease in children in Puerto Rico and the U.S. 

Publications and Presentations:

Publications have been submitted on this subproject: View all 11 publications for this subprojectView all 25 publications for this center

Journal Articles:

Journal Articles have been submitted on this subproject: View all 1 journal articles for this subprojectView all 10 journal articles for this center

Progress and Final Reports:

2016 Progress Report
2017 Progress Report


Main Center Abstract and Reports:

R836155    Center for Research on Early Childhood Exposure and Development in Puerto Rico

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R836155C001 Air Pollution Impacts on Neonatal and Early Childhood Development
R836155C002 Toxicogenomics-based Mechanistic Multimedia Exposure Assessment and Child Development
R836155C003 Biomarker Epidemiology of In Utero Environmental Exposures and Child Development